Hematopoietic stem cells comprise a very small fraction of bone marrow mononuclear cells, which retain the capacity for self-renewal as well as controlled differentiation into all the cellular elements of the peripheral blood. The molecular signals that confer the stem cell phenotype and the mechanisms that control stem cell proliferation and differentiation are incompletely understood. In preliminary work, we have identified a divergent homeobox gene that is expressed in murine hematopoietic stem/progenitor cells but not in differentiated cells. Our studies have demonstrated the expression of one or more novel mRNA isoforms of this gene in hematopoietic stem/progenitor cells and embryonic stem cells. The research goals of this proposal are to establish the role of this gene in hematopoiesis. Specifically, we propose to: investigate the genetic basis for the various isoforms of the gene, characterize the temporal and cell/tissue-specific pattern of expression of the gene and its product(s) in the mouse, and examine the effect of overexpression of the gene product(s) on hematopoietic progenitor cell growth and differentiation in vitro. The laboratory research will be performed by the principle investigator, Dr. Barbara Degar, in conjunction with a didactic program under the guidance of a sponsor, Dr. Bernard Forget, and an advisory committee. In addition to the scientific goals, a further objective of this proposal is that it serve as a vehicle for the development of the candidate into an independent and productive investigator in the area of molecular hematopoiesis.